pulmonary embolism an unsuspected killer

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Pulmonary embolism: an

unsuspected killer

Torrey A. Laack, MDa,b,c,d,*, Deepi G. Goyal, MDb,c

aDepartment of Pediatric and Adolescent Medicine, Mayo Medical School,

Mayo Clinic, 200 First Street SW, Rochester, MN 55905, USAbDepartment of Emergency Medicine, Mayo Medical School, Mayo Clinic,

200 First Street SW, Rochester, MN 55905, USAcMayo Emergency Medicine Residency, Mayo Medical School, Mayo Clinic,

200 First Street SW, Rochester, MN 55905, USAdDepartment of Pediatrics, Mayo Medical School, Mayo Clinic,

200 First Street SW, Rochester, MN 55905, USA

The accurate diagnosis of pulmonary embolism (PE) is crucial. PE is

currently the third leading cause of death in the United States with 50,000to 100,000 estimated deaths per year and an incidence of 0.5 to 1 per 1000

[14]. PE is a leading cause of unexpected deaths in hospitalized patients and

a major source of medical malpractice lawsuits[5]. However, the diagnosis is

missed more often than it is made. One author conservatively estimates that

more than half of fatal PE cases are not even suspected antemortem [6].

Prior autopsy studies consistently have shown the rate to be even higher, at

approximately 70%[711]. Conversely, in patients in whom the diagnosis is

considered, the prevalence of PE is only 25% to 35% [12,13]. Therefore,

clinicians generally miss PE when it is present and suspect it when it is not.PE is truly an unsuspected killer with profound clinical implications.

Although patients in whom PE is diagnosed and treated have a mortality

rate of only 3% to 8%[3,14,15], those in whom the diagnosis is missed have

a fourfold to sixfold greater mortality[3,6,15].

Before the use of heparin, surgical interventions were the only treatment

options available for PE with a mortality rate approaching 100% [16].

Heparin first was administered to treat PE in the 1930s, but concerns over its

safety in this setting prevented more widespread use. It was not until 1960

that the benefits of anticoagulation therapy were confirmed[17]. Beginning

* Corresponding author. Department of Emergency Medicine, Mayo Medical School,

Mayo Clinic, 200 First Street SW, Rochester, MN 55905, USA.

E-mail address: [email protected](T.A. Laack).

0733-8627/04/$ - see front matter 2004 Elsevier Inc. All rights reserved.

doi:10.1016/j.emc.2004.05.011

Emerg Med Clin N Am

22 (2004) 961983
http://-/?-mailto:[email protected]:[email protected]://-/?-


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in the 1960s, the use of fibrinolytics was studied; fibrinolytics were reserved

primarily for unstable patients with PE [16]. With the advent of effective

therapy, the accurate diagnosis of thromboembolic disease became vital.Although many deaths are attributed to undiagnosed pulmonary emboli,

the actual incidence of PE in the general population and the risk of

mortality or morbidity from an individual pulmonary embolus are un-

known. A high incidence of asymptomatic PE has been shown in patients

with deep venous thrombosis (DVT) [1822], suggesting that PE may be

common and only infrequently may lead to death. Although some studies

have found mortality rates from untreated PE ranging from 25% to 30%,

these studies involved patients with other comorbidities that likely

contributed to the adverse outcomes [17,23,24].Other studies involving pa-tients without coexisting cardiopulmonary disease have found that mortality

even with untreated or recurrent PE was significantly lower [22,2427].

A follow-up study of the untreated patients with PE from the Prospective

Investigation of Pulmonary Embolism Diagnosis (PIOPED) revealed

a mortality rate from PE of only 5% (1 in 20)[27].

Given the fact that anticoagulation carries with it significant bleeding

risks and that not all cases of PE cause morbidity or mortality, the risk of

misdiagnosis of PE is not limited to missing the diagnosis. Incorrectly diag-

nosing PE in patients in whom it is absent or inconsequential unnecessarilyexposes them to the risks inherent with long-term anticoagulation therapy.

Because the accurate diagnosis of PE is crucial to maximizing patient

outcomes, this article focuses on atypical presentations, unique challenges in

certain patient populations, and current diagnostic strategies for PE.

Background

Venous thromboembolism (VTE) is a disease with a spectrum of mani-

festations that include thrombophlebitis, DVT, and PE. Most pulmonaryemboli have their origin in clots in the iliac, deep femoral, or popliteal veins.

Pulmonary emboli also can originate from sources in the upper extremities,

central vascular access devices, heart, and vena caval filters[2830]. The site

of the DVT does not seem to be as important as previously was thought

because PE can occur from any site of DVT formation [31]. Calf vein

thrombosis, previously considered relatively benign, propagates above the

knee in approximately 80% and may cause PE without first extending

proximally[16].Likewise, although superficial thrombophlebitis is generally

benign, it can extend into the deep venous system and pose a risk for PE[32]. In many instances of PE, no peripheral source of thrombosis is ever

identified.

Virchow first described the process of thrombosis as involving a triad of

stasis, hypercoagulability, and endothelial injury [33]. Risk factors for PE

can be inherited or acquired (Box 1) and must be considered when

assessing a patients probability of PE[29,30,35]. The strongest risk factor of

962 T.A. Laack, D.G. Goyal / Emerg Med Clin N Am 22 (2004) 961983


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VTE seems to be a history of prior thromboembolic disease [35]. In

addition, malignancy and surgery are well known to be associated with

VTE. Certain malignancies, such as tumors affecting the lung, brain,

ovaries, and pancreas, are especially prone toward predisposing patients toVTE [29], as are neurosurgical and orthopedic surgical procedures [34].

Major trauma patients are a high-risk patient population that deserves

particular attention because PE is the third most common cause of death in

these patients [2,36]. One study of victims of major trauma revealed that

nearly 60% had a DVT, most of whom were asymptomatic[37].

Despite the clinical significance of risk factors for VTE, Morgenthaler

and Ryu[9]found that 12% (11 of 92) of patients with PE as the cause of

death at autopsy lacked any known risk factor. Risk factors must be taken

into account in conjunction with the patients history and presentation, butan absence of risk factors does not reliably exclude the diagnosis of PE.

Clinical presentation

The presentation of PE is occasionally dramatic, but more commonly

patients present with subtle clinical findings, or they may be completely

Box 1. Risk factors predisposing to venous thromboembolism

Inherited risk factorsAntithrombin III deficiency

Protein C deficiency

Protein S deficiency

Factor V Leiden mutation

Acquired risk factors

Prior history of venous thromboembolism

Malignancy

SurgeryTrauma

Central venous access devices

Pregnancy and the puerperium

Immobilization (travel, paralysis, bedridden state)

Congestive heart failure

Myocardial infarction

Stroke

Advanced age

SmokingObesity

Oral contraceptives/hormone replacement therapy

963T.A. Laack, D.G. Goyal / Emerg Med Clin N Am 22 (2004) 961983


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asymptomatic. This situation contributes to the large number of cases that

are missed on initial presentation. The classic findings of hemoptysis,

dyspnea, and chest pain are insensitive and nonspecific for a diagnosis ofPE, with fewer than 20% having this classic triad. The incidence of common

symptoms in patients suspected of having PE is depicted inTable 1[38].One

prospective observational study found that the single historical finding most

sensitive for PE was unexplained dyspnea. Even this finding was absent,

however, in 8% of the patients studied [39]. Although unexplained chest

pain or dyspnea always should lead to the consideration of PE, the fact that

presentations of PE are often subtle mandates that the clinician not over-

look the diagnosis based on a lack of these symptoms.

No single physical examination finding is sensitive or specific for PE.Table 1shows the prevalence of various signs in patients suspected of having

PE [38]. Although other studies reveal tachypnea to be the most sensitive

clinical sign, it is absent in 5% to 13% of cases of PE[34,40]. Tachycardia is

even less sensitive, especially in younger patients, with 70% of PE patients

younger than 40 years old and 30% of patients older than 40 having heart

rates less than 100 beats/min [40]. Fever tends to be low grade, and its

presence may mislead the clinician into suspecting an infectious etiology.

Table 1

Symptoms and signs in 500 patients with clinically suspected pulmonary embolism

PE present n=202 PE absent n = 298

No. % No. % P

Symptoms

Dyspnea (sudden onset) 158 78 87 29 \.00001

Dyspnea (gradual onset) 12 6 59 20 .00002

Orthopnea 2 1 27 9 .00004

Chest pain (pleuritic) 89 44 89 30 .002

Chest pain (substernal) 33 16 29 10 .04

Fainting 53 26 38 13 .0002

Hemoptysis 19 9 16 5 .12

Cough 22 11 45 15 .22

Palpitations 36 18 46 15 .56

Signs

Tachycardia[100/min 48 24 69 23 .96

Cyanosis 33 16 44 15 .73

Hypotension\90 mm Hg 6 3 5 2 .15

Neck vein distention 25 12 28 9 .36

Leg swelling (unilateral) 35 17 27 9 .009

Fever[38C 14 7 63 21 .00003

Crackles 37 18 76 26 .08

Wheezes 8 4 39 13 .001

Pleural friction rub 8 4 11 4 .93

Abbreviation:PE, pulmonary embolism.

From Miniati M, Prediletto R, Fromichi B, et al. Accuracy of clinical assessment in the

diagnosis of pulmonary embolism. Am J Respir Crit Care Med 1999;159:866; with permission.



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Stein et al[41]found fever with no other source present in 14% of patients

with PE.

Data from the PIOPED found that in patients diagnosed with PE, 97%had the presence of dyspnea, chest pain, or tachypnea[13]. Dyspnea, chest

pain, and tachypnea are all nonspecific symptoms, however, that are found

more commonly with diseases other than PE. This finding is likely subject to

considerable selection bias because only patients in whom the diagnosis was

suspected were enrolled in the PIOPED study, whereas patients with silent

or atypical presentations of PE would have been missed and their symptoms

not recorded. The symptoms of dyspnea, pleuritic chest pain, and tachypnea

are not only nonspecific, but also they may be insensitive when generalized

to all patients with PE[4].Patients traditionally have been described as having one of three classic

syndromes: pulmonary infarction, isolated dyspnea, or circulatory collapse.

This is an oversimplification of the clinical presentation of PE that does not

account for atypical presentations and occult pulmonary emboli. Patients in

whom the diagnosis is suspected tend to present, however, with one of these

three syndromes. Although one should not limit clinical suspicion only to

patients in these categories, it is extremely difficult to diagnose PE reliably in

patients outside of this simplified scheme.

Patients with pulmonary infarction commonly present with chest painsecondary to irritation of the pleura. It may be difficult to differentiate

between PE and pneumonitis or pleuritis. Hemoptysis usually is self-limited

and occurs in approximately one third of these patients. Pulmonary infarc-

tion is much more common in older patients with underlying cardiopul-

monary disease, and they tend to present with pleuritic chest pain more

frequently[30,42]. PE may be present in 20% of young patients, however,

without specific risk factors for VTE who present with a complaint of

pleuritic chest pain [16]. Pulmonary infarct is associated with submassive

and less severe PE than isolated dyspnea or circulatory collapse[42,43].In patients with isolated dyspnea, the severity of symptoms is related to

the degree of vascular obstruction and their underlying cardiopulmonary

reserve. Even with obstruction of 50%, patients may remain asymptomatic

[42]. PE may be difficult to distinguish from other causes of dyspnea, such as

congestive heart failure (CHF), hyperventilation, reactive airway disease, or

obstructive lung disease. Patients with circulatory collapse have the most

severe form of PE. They may present with syncope, hemodynamic in-

stability, or full cardiopulmonary arrest.

Atypical presentations

Atypical presentations of PE are common, with symptoms such as

abdominal pain, back pain, fever, cough, atrial fibrillation, and hiccoughs

[16]. As noted earlier, most fatal pulmonary emboli are never suspected and



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go undiagnosed. Many of these misses may involve patients with other sig-

nificant comorbid disease to which their symptoms are attributed incorrectly.

A significant percentage of these misses may be due to clinically silent oroccult presentations and pulmonary emboli causing sudden cardiopulmonary

arrest. Given that only a few cases of PE are suspected, these atypical

presentations seem to represent most fatal cases of PE. Atypical presentations

that are explored in more detail include occult PE, syncope, and PE in the

setting of cardiopulmonary arrest.

Occult PEs are known to exist in asymptomatic patients in high-risk

groups. Of asymptomatic surgical patients, 15% have been shown to have

evidence of PE on lung scans[24]. In patients with known DVT but without

symptoms suggesting PE, 40% to 60% have lung scan or angiogramfindings suggesting PE[1921]; this has led some authors to propose that all

patients diagnosed with DVT have a baseline ventilation-perfusion (V/Q)

scan[18,21]. Because the risk of recurrent VTE is low in patients adequately

treated and because of the unclear clinical significance of these abnormal V/

Q scans, other authors do not think that baseline lung scans are indicated

for all patients diagnosed with DVT [20,4446]. The rate of asymptomatic

PE in the general population or in patients with occult DVT is unknown. It

is possible that healthy individuals frequently have small emboli that

dissolve rapidly and never become symptomatic.Of patients presenting with syncope, Sarasin et al[47]found PE to be the

cause in about 1%. Meanwhile, syncope is present in 8% to 13% of all

patients with PE [48]. It is presumed to be secondary to right ventricular

outflow obstruction causing transient hypotension. In a study of 92 patients

at autopsy with PE as the cause of death, more than one quarter had a

history of syncope [9]. Patients with PE who present with syncope carry

a worse prognosis than patients who do not[48]; this may be due to the fact

that larger pulmonary emboli are necessary to cause the outflow obstruction

required to induce syncope. In a study by Bell et al[49], syncope occurred in20% of patients with massive PE compared with only 4% of patients with

submassive PE.

PE may cause right ventricular outflow obstruction with subsequent

decreased left ventricular filling and cardiac output, leading to hypotension,

shock, and cardiac arrest. One study found that of all patients presenting to

the emergency department in cardiac arrest, PE was responsible in 4.8%

[50]. In younger patients, who tend to have a lower baseline risk of cardiac

disease, the percentage of cardiac arrests due to PE is likely even higher,

with one author estimating it at 10%. In this study, patients with PE weremore likely to have pulseless electrical activity and witnessed arrest than

patients with other causes of death[51]. In another study, 63% of patients

with PE-induced cardiac arrest had pulseless electrical activity as the

presenting rhythm [52]. It is theorized that patients have time to seek aid

during a gradual progression to pulselessness with maintained electrical

activity. Conversely, in patients presenting with pulseless electrical activity



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and cardiac arrest, approximately one third to one half have been found to

have PE at autopsy[51,52].

Despite the frequency with which they occur, most missed PEs areunsuspected (Fig. 1)[4]. Some authorities argue, as expressed in an editorial

by Egermayer[53], There can be only a limited advantage to encouraging

increased alertness for a disease that is usually asymptomatic. Egermayers

recommendation was to place an increased emphasis on prevention rather

than diagnosis and treatment[53]. Although no amount of increased alert-

ness would allow a clinician to diagnose all cases of PE, it is only with

increased cognizance and development of improved diagnostic algorithms

that clinicians can enhance their ability to diagnose this deadly but treatable

disease.

Specific patient populations

Pediatrics

VTE in children usually is associated with hereditary or acquired co-

agulation abnormalities. Hereditary deficiencies include factor V Leiden

mutation; sickle cell disease; and deficiencies of protein C, protein S, and

antithrombin III. Thrombosis tends to be most pronounced in the neonatalperiod and at adolescence. There are numerous causes of acquired VTE,

including surgery, malignancy, trauma, central venous catheter placement,

infection, renal disease, autoimmune diseases, vasculitis, congenital heart

disease, and severe inflammatory bowel disease[54].Central vascular access

devices seem to be the most common acquired risk factor in children[55]. A

Fig. 1. Schema of relationship between suspected and actual cases of pulmonary embolism

(PE). (From Ryu JH, Olson EJ, Pellikka PA. Clinical recognition of pulmonary embolism:

problem of unrecognized and asymptomatic cases. Mayo Clin Proc 1998;73:877; with

permission.)



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retrospective study of 61 children with thrombosis found an association with

central vascular access in 25%[56].

Overall, VTE is rare in children. Rohrer et al[57]found an incidence oflower extremity DVT of only 0.05% (1 of 93 cases, in a 17-year-old) in

hospitalized children with at least two independent risk factors for

thrombosis. A study of pediatric intensive care unit patients found 4% to

have DVT [58], whereas at autopsy the rate of PE in children was ap-

proximately 4%[59]. A review of the literature on VTE in children revealed

that 98% had a precipitating factor, although it was not always known on

initial presentation[60]. Although rare, the diagnosis of PE should be con-

sidered in children manifesting suspicious symptoms, especially in older

children and children with risk factors. Children diagnosed with VTErequire anticoagulation and an extensive workup in search of a potential

underlying cause.

Pregnancy

PE is the leading cause of maternal mortality in developed countries

[61,62]. Although the incidence of PE in individuals older than age 45 is

higher in men than in women, numerous studies have shown that in young

adults, women have a significantly higher rate of PE[29]. Pregnancy and thepostpartum period are well-known risk factors for PE[63], with the risk of

PE five times higher in pregnant compared with nonpregnant women[34].

During the postpartum period, there is an even greater risk of thrombosis

than during pregnancy[29]. Although a high level of suspicion is necessary,

the prevalence of PE in pregnant patients in whom the diagnosis is

considered is quite low[64].

The diagnosis of PE in pregnancy is particularly difficult because dyspnea

may be a normal finding. Causes of dyspnea in pregnancy include upward

pressures on the diaphragm secondary to an intra-abdominal mass effectand increased oxygen consumption requiring increased cardiac output. By

the third trimester, 75% of pregnant women have dyspnea, and most women

have symptoms beginning by the 20th week. The physiologic dyspnea of

pregnancy may be difficult to differentiate from more worrisome causes such

as PE. Physiologic dyspnea tends to be mild without limiting daily activities,

it tends to be absent at rest, and it generally does not worsen as pregnancy

progresses. Symptoms such as syncope, hemoptysis, and chest pain should

not be attributed to physiologic dyspnea [65]. Likewise, dyspnea that has

a rapid onset should raise suspicion for PE.During pregnancy, failure to diagnose PE places the mother and the fetus

in jeopardy. Likewise, overdiagnosing PE places both patients at risk by

exposing them to anticoagulation and hospitalization. Although it is desir-

able to minimize fetal radiation exposure, the importance of making the

correct diagnosis mandates that the appropriate diagnostic studies be

performed. Although a negative D-dimer test can be helpful in patients with



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a low pretest probability of PE, it is not helpful in patients whose pretest

probability is estimated to be moderate or high. Because ultrasound poses no

risk to the fetus, bilateral lower extremity ultrasound is considered by someauthors to be the initial study of choice. If ultrasound is positive for DVT, PE

is implied, and the patient should be treated accordingly with no further

testing necessary. In pregnant patients being evaluated for PE without

specific symptoms of DVT, however, ultrasound is rarely positive[6668].

Many authorities advocate the use of V/Q scanning as the next step.

During pregnancy, especially in patients without prior history of pulmonary

disease, many scans are normal or near-normal in the absence of PE. The

radiation exposures from V/Q scan and chest x-ray are well below the

maximal recommended dose in pregnancy and can be decreased even furtherwithout compromising the study [62,64]. Although the use of helical CT

historically has been discouraged, there is increasing evidence that next-

generation CT scanners subject the patient to less radiation than does V/Q

scanning [69,70]. This evidence has led to the preferential use of CT over

V/Q scanning in pregnant patients at the authors institution. If pulmonary

angiography is required, the abdomen can be shielded in an attempt to

reduce radiation exposure to the fetus. If PE is discovered, warfarin is

contraindicated because it is a known teratogen [71], and the patient

requires admission and daily administration of unfractionated heparin orlow-molecular-weight heparin for the duration of pregnancy.

Elderly

Elderly patients are at an increased risk of developing PE, but it is unclear

if this is because age is an independent risk factor or secondary to a higher

prevalence of underlying disease and recent surgery in this patient popula-

tion. The mean age of patients presenting with PE is approximately 60 years

with a rate 10 times higher in patients older than 75 compared with patientsyounger than 40 [29,36]. Elderly patients with PE have higher mortality

compared with younger patients. The reason is multifactorial and likely due

to the fact that diagnosis is more difficult and the higher incidence of

underlying disease in this patient population. In addition, the elderly have

more bleeding complications from therapy with a resulting increased

likelihood of having anticoagulants withheld[28].

The specificity of some diagnostic tests is decreased in the elderly. The

specificity of D dimer was found to be 67% in patients younger than 40, but

only 10% in patients age 80 and older. In addition, the number of non-diagnostic V/Q scans increased from 32% to 58% in these same age groups

[72]. There is no single diagnostic test that is ideal for the diagnosis of PE

in elderly patients. When a diagnosis of VTE is made in an elderly patient, the

patient should be treated with anticoagulation unless he or she has a specific

contraindication. Age should not preclude thrombolytic therapy when

appropriate[73,74].



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definitive results. CT may help diagnose PE and alternative diagnoses, such

as pericardial effusion.

Although human immunodeficiency virus (HIV) infection is consideredby some to be a risk factor for PE secondary to the hypercoagulable state

associated with the infection, VTE is actually uncommon in HIV-positive

patients. Many HIV-positive patients present with symptoms due to

respiratory infections that are difficult to distinguish from PE. The diagnosis

of PE still should be considered in HIV-positive patients with presumed

respiratory infections who do not respond to antimicrobial therapy[76].

Diagnostic approach

Given the lack of a single diagnostic test or clinical finding with adequate

sensitivity and specificity, the diagnosis of PE generally involves in-

terpretation of multiple data points in light of the emergency physicians

assessment of an estimated pretest probability. The authors current method

of diagnosing PE relies heavily on subjective assessment of risk. In some

cases, the diagnosis is made easily, but many more cases require the treating

physician to make a diagnosis based on uncertain information.

The frustration of examiners was emphasized in a 1999 poll of 623

emergency physicians who identified the evaluation of PE as the clinical

problem that would benefit most from a decision rule[77]. A nonvalidated

decision rule was proposed in 1990 by the PIOPED investigators, who used

the pretest assessment of risk combined with results from V/Q scanning.

This rule allowed for the noninvasive diagnosis or exclusion of PE in only

a few patients, however, with most requiring angiography [13]. Studies at

academic and private hospitals have shown a poor compliance with the

PIOPED approach[24,78,79].

The PIOPED recommendations require interpretation of the V/Q result

in terms of pretest probability. Accurately assigning pretest probability can

be difficult, however. No scoring system was devised initially, and clinical

estimates of pretest probability have been met with considerable inter-

observer variability[80,81]. Siegel et al[81]reported instances in which the

same patient was assigned a low pretest probability of PE by one examiner

and high probability by another. Several algorithms have been devised to

address this problem. Two of the most popular scoring systems are the Wells

and Geneva criteria (Table 2)[8284].

Validation studies of these decision rules reveal that they are predictive of

which patients have PE[84,85]. They do not give definitive results, however,

or obviate the need for further diagnostic tests, and they have not been

proved to be superior to implicit clinical judgment. The prevalence of PE in

the population to which these rules are applied affects the success of these

scoring systems[84].These decision rules are best suited for risk stratifying

patients to estimate a pretest likelihood of PE before diagnostic studies.



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If one follows the PIOPED recommendations, most patients being

evaluated for PE require angiography. The rate of pulmonary angiography

performed in these patients is typically less than 12%, however, with most

physicians unwilling or unable to obtain angiography routinely in the

workup of PE [24,78,79,86,87]. Some authors believe that failure to obtain

angiography in all cases that have nondiagnostic studies is unacceptable due

to the likelihood of missed pulmonary emboli. Follow-up studies have

shown, however, that PE is unlikely in patients discharged after a low-

probability V/Q scan[26]. Wolfe and Hartsell[24]argued that an outcome-based approach is more important than diagnosis of all PE cases. They

pointed out that in patients with adequate cardiopulmonary reserve, occult

VTE not diagnosed by noninvasive testing does not seem to affect outcome

[24,25,82,88,89]. This situation has led to the formation of an alternative

algorithmic approach, which attempts to reduce the number of recom-

mended angiography studies (Fig. 2) [24]. Although currently lacking

Table 2

Prediction rules for suspected pulmonary embolism

Geneva score [13] Points Wells score [14] PointsPrevious pulmonary embolism or

deep vein thrombosis

2 Previous pulmonary embolism or

deep vein thrombosis

1.5

Heart rate[100 beats p/min 1 Heart rate[100 beats p/min 1.5

Recent surgery 3 Recent surgery or immobilization 1.5

Age (y) Clinical signs of deep vein

thrombosis

3

6079 1 Alternative diagnosis less likely than 3

80 2 pulmonary embolism

Hemoptysis 1

Cancer 1

PaCO2\4.8 pKa (36 mm Hg) 2

4.85.19 pKa (3638.9 mm Hg) 1

PaO2\6.5 pKa (48.7 mm Hg) 4

6.57.99 pKa (48.759.9 mm Hg) 3

89.49 pKa (6071.2 mm Hg) 2

9.510.99 pKa

(71.382.4 mm Hg)

1

Atelectasis 1

Elevated hemidiaphragm 1

Clinical probability Clinical probability

Low 04 Low 01

Intermediate 58 Intermediate 26

High 9 High 7

Abbreviations: PaO2, partial pressure of oxygen, arterial; PaCO2, partial pressure of carbon

dioxide, arterial.

From Chagnon I, Bounameaux H, Aujesky D, et al. Comparison of two clinical prediction

rules and implicit assessment among patients with suspected pulmonary embolism. Am J Med

2002;113:270; with permission.



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Fig. 2. Proposed diagnostic algorithm for the evaluation of suspected pulmonary embolism

(PE). CTA, computed tomography angiography; DVT, deep venous thrombosis; ELISA,

enzyme-linked immunosorbent assay; V/Q, ventilation-perfusion. (Adapted from Wolfe TR,

Hartsell SC. Pulmonary embolism: making sense of the diagnostic evaluation. Ann Emerg Med

2001;37:509; with permission.)



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prospective validation, such an algorithm better fits current practice and

avoids the need for angiograms in most patients.

Diagnostic tests

Electrocardiogram, arterial blood gas, chest radiography

Electrocardiogram, arterial blood gas analysis, and chest radiography all

have a limited role in the evaluation of PE. The primary utility of the

electrocardiogram is its ability to point to an alternate diagnosis, such as

acute coronary syndrome or pericarditis. Classic findings, such as S1Q3T3,

lack sensitivity and specificity (54% and 62%), whereas the most commonelectrocardiogram abnormality, found in 68%, is T-wave inversion in the

precordial leads[90]. Chest radiography similarly has its primary utility in

detecting alternative diagnoses, such as pneumothorax, CHF, and pneumo-

nia. Chest x-ray findings can be misleading, however, and must be inter-

preted carefully because findings suggesting CHF or pneumonia may coexist

with a pulmonary embolus. In a study of patients ultimately diagnosed with

PE, 76% of chest x-rays were abnormal, but the noted abnormalities tended

to be nonspecific [91]. Arterial blood gas analysis has a limited role in the

evaluation of PE. It is a relatively invasive procedure that lacks the sen-sitivity or specificity to rule in or out disease[92].

D dimer

D-dimer testing has been proposed by some authorities as a convenient,

noninvasive way to exclude or to increase suspicion for VTE. Specificity is

known to be low secondary to false-positive results from numerous causes,

such as trauma, postoperative state, sepsis, and myocardial infarction[30].

It also is less likely to be helpful in elderly patients and patients with sig-

nificant comorbid disease. The role of D dimer generally has been reservedfor ruling out disease in low-risk patients. Wells et al[93]found that patients

with a low clinical probability of VTE and a negative D-dimer assay could

be discharged safely with only 0.4% found to have VTE on follow-up

examination. However, The numerous different assays available and insti-

tutional variability in terms of the assays used have led to confusion and

precluded the universal adoption of D-dimer assays as screening tests for

PE. Readers are referred to a review by Sadosty et al [94] for a more in-

depth analysis of D-dimer assays and to a meta-analysis by Brown et al[95]

regarding enzyme-linked immunosorbent assay D-dimer testing.

Ventilation-perfusion scintigraphy

V/Q is a two-part study involving a ventilation and a perfusion phase. A

radioisotope is injected, and areas of pulmonary perfusion are identified

using a gamma camera. A radiopharmaceutical is inhaled to identify areas



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of ventilation. The areas of perfusion and ventilation are compared to

identify foci of mismatch. Areas with ventilation but without perfusion

increase the suspicion for PE because thrombus obstruction of a pulmonaryartery would cause hypoperfusion to the affected lung segment without

affecting ventilation. The test must be interpreted in light of the patients

pretest probability. It is most helpful when there is concordance between the

pretest probability and the scan results (ie, a low pretest probability and

a normal/near-normal scan or a high pretest probability with a high

probability study (Table 3)[96]. Interpreting the study without factoring in

the pretest probability would lead to overdiagnosis and underdiagnosis of

PE: Of patients who have a high-probability V/Q scan but a low pretest

probability, 44% would have angiograms negative for PE, whereas inpatients with a low-probability scan but a high pretest probability, 40%

would be found to have PE on angiogram (seeTable 3)[13,96]. Because of

these interpretive factors and because patients with preexisting lung disease

often have abnormal studies, V/Q scan provides a definitive answer

regarding whether or not a patient should be started on anticoagulation

therapy in only 25% to 40% of cases[12].

Spiral computed tomography

CT is becoming increasingly accepted in the evaluation of PE. Fig. 3

shows a large proximal pulmonary embolus in the pulmonary artery. CT is

rapid, noninvasive, and widely available. It is more likely to be diagnostic

than V/Q scanning and is less expensive than V/Q scanning, magnetic

resonance angiography, and pulmonary angiography. CT also has the

advantage of being able to elucidate alternative diagnoses, such as infectious

or neoplastic processes. Its primary limitations relate to the need for

potentially nephrotoxic intravenous contrast material, which is contra-

indicated in patients with a contrast allergy or renal failure. Many

investigators have questioned whether the sensitivity of CT is sufficient to

Table 3

Clinical assessment and ventilation-perfusion scan probability in PIOPED*

Clinical probabilityVentilation-perfusion

scan (probability) High likely (80100%) Uncertain (2079%) Unlikely (019%)

High 28/29y (96%) 70/80 (88%) 5/9 (56%)

Intermediate 27/41 (66%) 66/236 (28%) 11/68 (16%)

Low 6/15 (40%) 30/191 (16%) 4/90 (4%)

Near-normal/normal 0/5 (0%) 4/62 (6%) 1/61 (2%)

Total 61/90 (68%) 170/569 (30%) 21/228 (9%)

* PIOPED = Prospective Investigation of Pulmonary Embolism Diagnosis.y Number of patients with proven pulmonary embolism per number of patients with the

specific scan result.

From American Thoracic Society. The diagnostic approach to acute venous thromboem-

bolism: clinical practice guideline. Am J Respir Crit Care Med 1999;160:1055; with permission.



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rule out definitively the possibility of PE [97]. Perrier et al [12] found the

sensitivity and specificity to be only 70% and 91%, whereas others havereported sensitivities of 88% to 100% with negative predictive values of

89% to 95%[98100].

Despite its potential promise, the role of CT in the diagnosis of PE is not

clear. Isolated subsegmental emboli and horizontal vessels are not visualized

well on CT, and lymph nodes may be misinterpreted as emboli with false-

positive results [24,30,69]. Subsegmental emboli are not visualized well on

angiogram either [24,101]. Newer thin-collimation multislice CT scanners

have increased speed and allow improved visualization with less motion

artifact [68]. The clinical significance of isolated subsegmental emboli isuncertain and has been questioned [102]. If these emboli are not clinically

important, failed diagnosis would be beneficial because unnecessary anti-

coagulation therapy could be avoided. However, If subsegmental emboli are

clinically relevant, false-negative results could lead to poor outcomes or

possible untoward future events.

Three studies have concluded that withholding anticoagulant therapy on

the basis of a negative helical CT scan is safe [100,102,103]. Swensen et al

[99]and Donato et al[102]found that only 8 of 993 and 4 of 239 patients

developed VTE within 3 months of a negative CT scan. In patients with CTresults negative for PE, there were 189 deaths (118, 33, and 38 deaths in the

Swenson et al[100], Donato et al[102],and van Strijen et al[102]studies),

with only 5 of these deaths thought to be secondary to PE. Whether occult

PE played a role in the remaining 184 deaths is unknown but could affect

significantly the data interpretation. These studies used superior CT tech-

nology and experienced radiologic interpretation that may not be available

Fig. 3. Pulmonary embolus (PE) located in the proximal pulmonary artery (PA) as seen on

spiral CT.



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nature or by leading to rapid death from cardiopulmonary arrest. In pa-

tients who do manifest symptoms from PE, accurate diagnosis is essential.

Often it is difficult to distinguish the vague symptoms of PE from otherdiagnoses, such as acute coronary syndrome, pneumonia, COPD, CHF,

aortic dissection, myocarditis or pericarditis, pneumothorax, and musculo-

skeletal or gastrointestinal causes. Regardless of the presentation, the most

fundamental step in making the diagnosis of PE is first to consider it.

Historical clues and risk factors should raise the clinicians suspicion.

PE is an unsuspected killer with a nebulous presentation and high mor-

tality. In all likelihood, PE will remain an elusive diagnosis despite advances

in technology and a wealth of research. A high index of suspicion is required,

but no amount of suspicion would eliminate all missed cases. Patients withsignificant underlying cardiopulmonary disease seem to be the most chal-

lenging. Patients with significant comorbidity have poor reserve and are

likely to have poor outcomes, especially if the diagnosis is not made and

anticoagulation is not initiated early.

Controversy exists over the best diagnostic approach to PE. A battery of

diagnostic studies is available, with few providing definitive answers. Studies

such as CT may be helpful at some institutions but offer poor predictive

value at others. Other diagnostic tests are not universally available. It is

hoped that further research and improvements in current diagnostic modal-ities will clear some of the current confusion and controversy of this

ubiquitous and deadly disease.

Acknowledgments

The authors thank Judith Roberson and Dr. Nadia Laack, for their

assistance in the preparation of this article.

References

[1] Gillum RF. Pulmonary embolism in the United States, 19701985. Am Heart J 1987;113:

12624.

[2] Heit JA, Silverstein MD, Mohr DN, Petterson TM, Lohse CM, OFallon WM, et al. The

epidemiology of venous thromboembolism in the community. Thromb Haemost 2001;

86:45263.

[3] Rodger M, Wells PS. Diagnosis of pulmonary embolism. Thromb Res 2001;103:V22538.

[4] Ryu JH, Olson EJ, Pellikka PA. Clinical recognition of pulmonary embolism: problem of

unrecognized and asymptomatic cases. Mayo Clin Proc 1998;73:8739.

[5] Tapson VF. Prophylaxis strategies for patients with acute venous thromboembolism. Am

J Manag Care 2001;7(17 Suppl):S52434.

[6] Pineda LA, Hathwar VS, Grant BJ. Clinical suspicion of fatal pulmonary embolism. Chest

2001;120:7915.

[7] Goldhaber SZ, Hennekens CH, Evans DA, Newton EC, Godleski JJ. Factors associated

with correct antemortem diagnosis of major pulmonary embolism. Am J Med 1982;73:

8226.



19/23

[8] Karwinski B, Svendsen E. Comparison of clinical and postmortem diagnosis of pulmonary

embolism. J Clin Pathol 1989;42:1359.

[9] Morgenthaler TI, Ryu JH. Clinical characteristics of fatal pulmonary embolism in a referral

hospital. Mayo Clin Proc 1995;70:41724.

[10] Rubenstein I, Murray D, Hoffstein V. Fatal pulmonary emboli in hospitalized patients: an

autopsy study. Arch Intern Med 1988;148:14256.

[11] Stein PD, Henry JW. Prevalence of acute pulmonary embolism among patients in a general

hospital and at autopsy. Chest 1995;108:97881.

[12] Perrier A, Howarth N, Didier D, et al. Performance of helical computed tomography in

unselected outpatients with suspected pulmonary embolism. Ann Intern Med 2001;135:

8897.

[13] PIOPED Investigators. Value of the ventilation/perfusion scan in acute pulmonary emb-

olism: results of the prospective investigation of pulmonary embolism diagnosis (PIOPED).

JAMA 1990;263:27539.

[14] Alpert JS, Smith R, Carlson CJ, Ockene IS, Dexter L, Dalen JE. Mortality in patients

treated for pulmonary embolism. JAMA 1976;236:147780.

[15] Carson JL, Kelley MA, Duff A, et al. The clinical course of pulmonary embolism. N Engl

J Med 1992;326:12405.

[16] Feied CF. Venous thrombosis and pulmonary embolism. In: Rosens emergency medicine

concepts and clinical practice. Marx JA, Hockberger RS, Walls RM, Adams J,

Barkin RM, Barsan WG, et al, editors. 5th edition. Atlanta: Mosby; 2002. p. 121034.

[17] Barritt DW, Jordan SC. Anticoagulant drugs in the treatment of pulmonary embolism:

a controlled trial. Lancet 1960;1:130912.

[18] Dorfman GS, Cronan JJ, Tupper TB, Messersmith RN, Denny DF, Lee CH. Occult

pulmonary embolism: a common occurrence in deep venous thrombosis. AJR AmJ Roentgenol 1987;148:2636.

[19] Huisman MV, Bu ller HR, ten Cate JW, van Royen EA, Vreeken J, Kersten MJ, et al.

Unexpected high prevalence of silent pulmonary embolism in patients with deep venous

thrombosis. Chest 1989;95:498502.

[20] Meignan M, Rosso J, Gauthier H, et al. Systemic lung scans reveal a high frequency of silent

pulmonary embolism in patients with proximal deep venous thrombosis. Arch Intern Med

2000;160:15964.

[21] Moser KM, Fedullo PF, LittleJohn JK, Crawford R. Frequent asymptomatic pulmonary

embolism in patients with deep venous thrombosis. JAMA 1994;271:2235.

[22] Nielson HK, Husted SE, Krusell LR, Fasting H, Charles P, Hansen HH. Silent pulmonary

embolism in patients with deep venous thrombosis: incidence and fate in a randomized,controlled trial of anticoagulation versus no anticoagulation. J Intern Med 1994;235:

45761.

[23] Dalen JE, Alpert JS. Natural history of pulmonary embolism. Prog Cardiovasc Dis 1975;

17:25970.

[24] Wolfe TR, Hartsell SC. Pulmonary embolism: making sense of the diagnostic evaluation.

Ann Emerg Med 2001;37:50414.

[25] Hull RD, Raskob GE, Pineo GF, Brant RF. The low-probability lung scan: a need for

change in nomenclature. Arch Intern Med 1995;155:184551.

[26] Rajendram JG, Jacobson AF. Review of 6-month mortality following low-probability lung

scans. Arch Intern Med 1999;159:34952.

[27] Stein PD, Henry JW, Relyea B. Untreated patients with pulmonary embolism: outcome,clinical, and laboratory assessment. Chest 1995;107:9315.

[28] Berman AR. Pulmonary embolism in the elderly. Clin Geriatr Med 2001;17:10730.

[29] Kim V, Spandorfer J. Epidemiology of venous thromboembolic disease. Emerg Med Clin

North Am 2001;19:83959.

[30] Sadosty AT, Boie ET, Stead LG. Pulmonary embolism. Emerg Med Clin North Am 2003;

21:36384.



20/23

[31] Lusiani L, Visona A, Bonanome A, Pesavento R, Zanco P. The characteristics of the

thrombi of the lower limbs, as detected by ultrasonic scanning, do not predict pulmonary

embolism. Chest 1996;110:9961000.

[32] Blumenberg RM, Barton E, Gelfand ML, Skudder P, Brennan J. Occult deep venous

thrombosis complicating superficial thrombophlebitis. J Vasc Surg 1998;27:33843.

[33] Virchow RLK. Cellular pathology as based upon physiological and pathohistology. 7th

American ed. Chance F, DeWitt RM, trans. New York, NY: 1860;236.

[34] National Institutes of Health. Prevention of venous thrombosis and pulmonary embolism.

JAMA 1986;256:7449.

[35] Colucciello SA. Protocols for deep venous thrombosis (DVT): a state-of-the-art review:

Part I. risk factor assessment, physical examination, and current diagnostic modalities.

Emerg Med Rep 2000;1324.

[36] Martinelli I. Risk factors in venous thromboembolism. Thromb Haemost 2001;86:

395403.

[37] Geerts WH, Code KI, Jay RM, Chen E, Szalai JP. A prospective study of venous

thromboembolism after major trauma. N Engl J Med 1994;331:16016.

[38] Miniati M, Prediletto R, Fromichi B, et al. Accuracy of clinical assessment in the diagnosis

of pulmonary embolism. Am J Respir Crit Care Med 1999;159:86471.

[39] Susec O, Boudrow D, Kline JA. The clinical features of acute pulmonary embolism in

ambulatory patients. Acad Emerg Med 1997;4:8917.

[40] Green RM, Meyer TJ, Dunn M, Glassroth J. Pulmonary embolism in younger adults.

Chest 1992;101:150711.

[41] Stein PD, Afzal A, Henry JW, Villareal CG. Fever in acute pulmonary embolism. Chest

2000;117:3942.

[42] Riedel M. Acute pulmonary embolism: 1. pathophysiology, clinical presentation, anddiagnosis. Heart 2001;85:22940.

[43] Stein PD, Henry JW. Clinical characteristics of patients with acute pulmonary embolism

stratified according to their presenting syndromes. Chest 1997;112:9749.

[44] Blebea J, Ewald S. Asymptomatic pulmonary embolism complicating deep venous

thrombosis. JAMA 1994;272:5178.

[45] Douketis JD, Kearon C, Bates S, Duku EK, Ginsberg JS. Risk of fatal pulmonary

embolism in patients with treated venous thromboembolism. JAMA 1998;279:45862.

[46] Stein PD. Silent pulmonary embolism. Arch Intern Med 2000;160:1456.

[47] Sarasin FP, Louis-Simonet M, Carballo D, et al. Prospective evaluation of patients with

syncope: a population-based study. Am J Med 2001;111:17784.

[48] Brilakis ES, Tajik AJ. 82-year-old man with recurrent syncope. Mayo Clin Proc 1999;74:60912.

[49] Bell WR, Simon TL, DeMets DL. The clinical features of submassive and massive

pulmonary emboli. Am J Med 1977;62:35560.

[50] Ku rkciyan I, Meron G, Sterz F, et al. Pulmonary embolism as cause of cardiac arrest. Arch

Intern Med 2000;160:152935.

[51] Courtney DM, Sasser HC, Pincus CL, Kline JA. Pulseless electrical activity with witnessed

arrest as a predictor of sudden death from massive pulmonary embolism in outpatients.

Resuscitation 2001;49:26572.

[52] Comess KA, DeRook FA, Russell ML, Tognazzi-Evans TA, Beach KW. The incidence of

pulmonary embolism in unexplained sudden cardiac arrest with pulseless electrical activity.

Am J Med 2000;109:3516.[53] Egermayer P. Silent pulmonary embolism. Arch Intern Med 2000;160:2218.

[54] Farrell SE. Special situations: pediatric, pregnant, and geriatric patients. Emerg Med Clin

North Am 2001;19:101323.

[55] Hoppe C, Matsunaga A. Pediatric thrombosis. Pediatr Clin North Am 2002;49:125783.

[56] Nuss R, Hays T, Manco-Johnson M. Childhood thrombosis. Pediatrics 1995;96:2914.



21/23

[57] Rohrer MJ, Cutler BS, MacDougall E, Herrmann JB, Anderson FA Jr, Wheeler HB.

A prospective study of the incidence of deep venous thrombosis in hospitalized children.

J Vasc Surg 1996;24:4650.

[58] DeAngelis GA, McIlhenny J, Willson DF, Vittone S, Dwyer SJ, Gibson JC, et al.

Prevalence of deep venous thrombosis in the lower extremities of children in the intensive

care unit. Pediatr Radiol 1996;26:8214.

[59] Buck JR, Connors RH, Coon WW, Weintraub WH, Wesley JR, Coran AG. Pulmonary

embolism in children. J Pediatr Surg 1981;16:38591.

[60] David M, Andrew M. Venous thromboembolic complications in children. J Pediatr 1993;

123:33746.

[61] de Swiet M. Management of pulmonary embolus in pregnancy. Eur Heart J 1999;20:

137885.

[62] Greer IA. The acute management of venous thromboembolism in pregnancy. Curr Opin

Obstet Gynecol 2001;13:56775.

[63] Danilenko-Dixon DR, Heit JA, Silverstein MD, Yawn BP, Petterson TM, Lohse CM, et al.

Risk factors for deep vein thrombosis and pulmonary embolism during pregnancy or post

partum: a population-based, case control study. Am J Obstet Gynecol 2001;184:10410.

[64] Kearon C. Diagnosis of pulmonary embolism. Can Med Assoc J 2003;168:18394.

[65] Gordon MC. Maternal physiology in pregnancy. In: Gabbe SG, Niebyl JR, Simpson JL,

editors. Obstetrics: normal and problem pregnancies. 4th edition. Philadelphia: Churchill

Livingstone; 2002. p. 6970.

[66] Daniel KR, Jackson RE, Kline JA. Utility of lower extremity venous ultrasound scanning

in the diagnosis and exclusion of pulmonary embolism in outpatients. Ann Emerg Med

2000;35:54754.

[67] Kearon C, Ginsberg JS, Hirsch J. The role of venous ultrasonography in the diagnosis ofsuspected deep venous thrombosis and pulmonary embolism. Ann Intern Med 1998;129:

10449.

[68] Turkstra F, Kuijer PM, van Beek EJ, Brandjes DP, ten Cate JW, Buller HR. Diagnostic

utility of ultrasonography of leg veins in patients suspected of having pulmonary embolism.

Ann Intern Med 1997;126:77581.

[69] Remy-Jardin M, Mastora I, Remy J. Pulmonary embolus imaging with multislice CT.

Radiol Clin North Am 2003;41:50719.

[70] Winer-Muram HT, Boone JM, Brown HL, Jennings SG, Mabie WC, Lombardo GT.

Pulmonary embolism in pregnant patients: fetal radiation dose with helical CT. Radiology

2002;224:48792.

[71] Andres RL, Miles A. Venous thromboembolism and pregnancy. Obstet Gynecol ClinNorth Am 2001;28:61330.

[72] Righini M, Goehring C, Bounameaux H, Perrier A. Effects of age on the performance

of common diagnostic tests for pulmonary embolism. Am J Med 2000;109:35761.

[73] Berman AR, Arnsten JH. Diagnosis and treatment of pulmonary embolism in the elderly.

Clin Geriatr Med 2003;19:15775.

[74] Gisselbrecht M, Diehl J, Meyer G, Collignon MA, Sors H. Clinical presentation and results

of thrombolytic therapy in older patients with massive pulmonary embolism: a comparison

with non-elderly patients. J Am Geriatr Soc 1996;44:18993.

[75] Stebbings AE, Lim TK. A patient with acute exacerbation of COPD who did not respond

to conventional treatment. Chest 1998;114:175961.

[76] Howling SJ, Shaw PJ, Miller RF. Acute pulmonary embolism in patients with HIV. SexTransm Infect 1999;75:259.

[77] Graham I, Stiell IG, McAuley L, et al. Potential areas for new clinical decision rules:

comparison of North American and Europe. Acad Emerg Med 1999;6:433.

[78] Murchison JT, Gavan DR, Reid JH. Clinical utilization of the non-diagnostic lung

scintigram. Clin Radiol 1997;52:2958.



22/23

[79] Rosen MP, Rose K, Davis RB. Work-up of patients with malignancy after an intermediate-

probability ventilation-perfusion scan: why dont physicians pursue a definitive diagnosis?

Acad Radiol 1997;4:80611.

[80] Jackson RE, Rudoni RR, Pascual R. Emergency physician (EP) assessment of the pre-test

probability of pulmonary embolism. Acad Emerg Med 1999;6:437.

[81] Siegel AH, Lebanon NH, Bettmann MA, Krone SM, Brokaw FC, Gerber PD, et al.

Interobserver variability in the clinical prediction of pulmonary embolus. Radiology 1997;

205:528.

[82] Wells PS, Ginsberg JS, Anderson DR, et al. Use of a clinical model for safe manage

ment of patients with suspected pulmonary embolism. Ann Intern Med 1998;129:

9971005.

[83] Wicki J, Perneger TV, Junod AF, Bounameaux H, Perrier A. Assessing clinical probability

of pulmonary embolism in the emergency ward. Arch Intern Med 2001;161:927.

[84] Chagnon I, Bounameaux H, Aujesky D, et al. Comparison of two clinical prediction rules

and implicit assessment among patients with suspected pulmonary embolism. Am J Med

2002;113:26975.

[85] Wells PS, Anderson DR, Rodger M, et al. Excluding pulmonary embolism at the bedside

without diagnostic imaging: management of patients with suspected pulmonary embolism

presenting to the emergency department by using a simple clinical model and D-dimer. Ann

Intern Med 2001;135:98107.

[86] Khorasani R, Gudas TF, Nikpoor N, Polak JF. Treatment of patients with suspected

pulmonary embolism and intermediate-probability lung scans: is diagnostic imaging

underused? AJR Am J Roentgenol 1997;169:13557.

[87] Saro G, Campo JF, Herna ndez MJ, Anta M, Olmos JM, Gonza les-Macas J, et al.

Diagnostic approach to patients with suspected pulmonary embolism: a report from thereal world. Postgrad Med J 1999;75:2859.

[88] Hull RD, Raskob GE, Ginsberg JS, et al. A noninvasive strategy for the treatment of

patients with suspected pulmonary embolism. Arch Intern Med 1994;154:28997.

[89] Perrier A, Desmarais S, Miron MJ, et al. Non-invasive diagnosis of venous thromboem-

bolism in outpatients. Lancet 1999;353:1905.

[90] Ferrari E, Imbert A, Chevalier T, Mihoubi A, Morand P, Baudouy M. The ECG in

pulmonary embolism: predictive value of negative T waves in precordial leads80 case

reports. Chest 1997;111:53743.

[91] Elliott CG, Goldhaber SZ, Visani L, DeRosa M. Chest radiographs in acute pulmonary

embolism. Chest 2000;118:338.

[92] Weiner SG, Burstein JL. Nonspecific tests for pulmonary embolism. Emerg Med ClinNorth Am 2001;19:94355.

[93] Wells PS, Anderson DR, Rodger M, et al. Evaluation of D-dimer in the diagnosis of

suspected deep-vein thrombosis. N Engl J Med 2003;349:122735.

[94] Sadosty AT, Goyal DG, Boie ET, et al. Emergency department D-dimer testing. J Emerg

Med 2001;21:4239.

[95] Brown MD, Rowe BH, Reeves MJ, Bermingham JM, Goldhaber SZ. The accuracy of the

enzyme-linked immunosorbent assay D-dimer test in the diagnosis of pulmonary

embolism: a meta-analysis. Ann Emerg Med 2002;40:13344.

[96] American Thoracic Society. The diagnostic approach to acute venous thromboembolism:

clinical practice guideline. Am J Respir Crit Care Med 1999;160:104366.

[97] Rathbun SW, Raskob GE, Whitsett TL. Sensitivity and specificity of helical computedtomography in the diagnosis of pulmonary embolism: a systematic review. Ann Intern Med

2000;132:22732.

[98] Holbert JM, Costello P, Federle MP. Role of spiral computed tomography in the diag-

nosis of pulmonary embolism in the emergency department. Ann Emerg Med 1999;33:

5208.



23/23

[99] Remy-Jardin M, Remy J, Deschildre F, et al. Diagnosis of pulmonary embolism with spiral

CT: comparison with pulmonary angiography and scintigraphy. Radiology 1996;200:

699706.

[100] Swensen SJ, Sheedy PF II, Ryu JH, Pickett DD, Schleck CD, Ilstrup DM, et al. Outcomes

after withholding anticoagulation from patients with suspected acute pulmonary embolism

and negative computed tomographic findings: a cohort study. Mayo Clin Proc 2002;77:

1308.

[101] Diffin DC, Leyendecker JR, Johnson SP, et al. Effect of anatomic distribution of pulmonary

emboli on interobserver agreement in the interpretation of pulmonary angiography. AJR

Am J Roentgenol 1998;171:10859.

[102] Donato AA, Scheirer JJ, Atwell MS, et al. Clinical outcomes in patients with suspected

acute pulmonary embolism and negative helical computed tomographic results in whom

anticoagulation was withheld. Arch Intern Med 2003;163:20338.

[103] Van Strijen MJL, de Monye W, Schiereck J, et al. Single-detector helical computed

tomography as the primary diagnostic test in suspected pulmonary embolism: a multicenter

clinical management study of 510 patients. Ann Intern Med 2003;138:30714.

[104] Stein PD, Athanasoulis C, Alavi A, et al. Complications and validity of pulmonary

angiography in acute pulmonary embolism. Circulation 1992;85:4628.

[105] Oudkerk M, van Beek EJ, Wielopolski P, van Ooijen PM, Brouwers-Kuyper EM,

Bongaerts AH, et al. Comparison of contrast-enhanced magnetic resonance angiography

and conventional pulmonary angiography for the diagnosis of pulmonary embolism:

a prospective study. Lancet 2002;359:16437.

[106] Kline JA, Kubin AK, Patel MM, Easton EJ, Seupal RA. Alveolar dead space as a predictor

of severity of pulmonary embolism. Acad Emerg Med 2000;7:6117.


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